Kaplan Samantha R, Oosthuizen Christa, Stinson Kathryn, Little Francesca, Euvrard Jonathan, Schomaker Michael, Osler Meg, Hilderbrand Katherine, Boulle Andrew, Meintjes Graeme
Yale School of Medicine, New Haven, Connecticut, United States of America.
Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
PLoS Med. 2017 Nov 7;14(11):e1002407. doi: 10.1371/journal.pmed.1002407. eCollection 2017 Nov.
Retention in care is an essential component of meeting the UNAIDS "90-90-90" HIV treatment targets. In Khayelitsha township (population ~500,000) in Cape Town, South Africa, more than 50,000 patients have received antiretroviral therapy (ART) since the inception of this public-sector program in 2001. Disengagement from care remains an important challenge. We sought to determine the incidence of and risk factors associated with disengagement from care during 2013-2014 and outcomes for those who disengaged.
We conducted a retrospective cohort study of all patients ≥10 years of age who visited 1 of the 13 Khayelitsha ART clinics from 2013-2014 regardless of the date they initiated ART. We described the cumulative incidence of first disengagement (>180 days not attending clinic) between 1 January 2013 and 31 December 2014 using competing risks methods, enabling us to estimate disengagement incidence up to 10 years after ART initiation. We also described risk factors for disengagement based on a Cox proportional hazards model, using multiple imputation for missing data. We ascertained outcomes (death, return to care, hospital admission, other hospital contact, alive but not in care, no information) after disengagement until 30 June 2015 using province-wide health databases and the National Death Registry. Of 39,884 patients meeting our eligibility criteria, the median time on ART to 31 December 2014 was 33.6 months (IQR 12.4-63.2). Of the total study cohort, 592 (1.5%) died in the study period, 1,231 (3.1%) formally transferred out, 987 (2.5%) were silent transfers and visited another Western Cape province clinic within 180 days, 9,005 (22.6%) disengaged, and 28,069 (70.4%) remained in care. Cumulative incidence of disengagement from care was estimated to be 25.1% by 2 years and 50.3% by 5 years on ART. Key factors associated with disengagement (age, male sex, pregnancy at ART start [HR 1.58, 95% CI 1.47-1.69], most recent CD4 count) and retention (ART club membership, baseline CD4) after adjustment were similar to those found in previous studies; however, notably, the higher hazard of disengagement soon after starting ART was no longer present after adjusting for these risk factors. Of the 9,005 who disengaged, the 2 most common initial outcomes were return to ART care after 180 days (33%; n = 2,976) and being alive but not in care in the Western Cape (25%; n = 2,255). After disengagement, a total of 1,459 (16%) patients were hospitalized and 237 (3%) died. The median follow-up from date of disengagement to 30 June 2015 was 16.7 months (IQR 11-22.4). As we included only patient follow-up from 2013-2014 by design in order to maximize the generalizability of our findings to current programs, this limited our ability to more fully describe temporal trends in first disengagement.
Twenty-three percent of ART patients in the large cohort of Khayelitsha, one of the oldest public-sector ART programs in South Africa, disengaged from care at least once in a contemporary 2-year period. Fifty-eight percent of these patients either subsequently returned to care (some "silently") or remained alive without hospitalization, suggesting that many who are considered "lost" actually return to care, and that misclassification of "lost" patients is likely common in similar urban populations. A challenge to meeting ART retention targets is developing, testing, and implementing program designs to target mobile populations and retain them in lifelong care. This should be guided by risk factors for disengagement and improving interlinkage of routine information systems to better support patient care across complex care platforms.
坚持治疗是实现联合国艾滋病规划署“90 - 90 - 90”艾滋病治疗目标的重要组成部分。自2001年南非开普敦的公共部门项目启动以来,在Khayelitsha镇(人口约50万),已有超过5万名患者接受了抗逆转录病毒治疗(ART)。治疗中断仍是一个重要挑战。我们试图确定2013 - 2014年期间治疗中断的发生率及相关风险因素,以及中断治疗者的结局。
我们对2013 - 2014年期间就诊于Khayelitsha的13家ART诊所中任何一家的所有≥10岁患者进行了一项回顾性队列研究,无论其开始ART的日期如何。我们使用竞争风险方法描述了2013年1月1日至2014年12月31日期间首次中断治疗(>180天未就诊)的累积发生率,这使我们能够估计ART启动后长达10年的中断治疗发生率。我们还基于Cox比例风险模型描述了中断治疗的风险因素,对缺失数据使用多重填补法。我们利用全省健康数据库和国家死亡登记处确定了中断治疗后至2015年6月30日的结局(死亡、恢复治疗、住院、其他医院接触、存活但未接受治疗、无信息)。在符合我们纳入标准的39,884名患者中,到2014年12月31日接受ART的中位时间为33.6个月(四分位间距12.4 - 63.2)。在整个研究队列中,592名(1.5%)患者在研究期间死亡,1,231名(3.1%)正式转出,987名(2.5%)为隐性转出并在180天内就诊于西开普省的另一家诊所,9,005名(22.6%)中断治疗,28,069名(70.4%)仍在接受治疗。接受ART治疗2年时,治疗中断的累积发生率估计为25.1%,5年时为50.3%。调整后与中断治疗相关的关键因素(年龄、男性、开始ART时怀孕[风险比1.58,95%置信区间1.47 - 1.69]、最近的CD4计数)和留存相关因素(ART俱乐部成员身份、基线CD4)与先前研究中发现的相似;然而,值得注意的是,在调整这些风险因素后,开始ART后不久中断治疗的较高风险不再存在。在9,005名中断治疗的患者中,最常见的两个初始结局是180天后恢复ART治疗(33%;n = 2,976)以及存活但未在西开普接受治疗(25%;n = 2,255)。中断治疗后,共有1,459名(16%)患者住院,237名(3%)死亡。从中断治疗日期到2015年6月30日的中位随访时间为16.7个月(四分位间距11 - 22.4)。由于我们按设计仅纳入了2013 - 2014年的患者随访情况,以便最大限度地将我们的研究结果推广到当前项目,这限制了我们更全面描述首次中断治疗时间趋势的能力。
在南非历史最悠久的公共部门ART项目之一、Khayelitsha的一大群ART患者中,23%的患者在当代2年期间至少有一次中断治疗。这些患者中有58%随后要么恢复治疗(一些是“隐性”恢复),要么存活且未住院,这表明许多被视为“失访”的患者实际上恢复了治疗,并且在类似城市人群中,“失访”患者的误分类可能很常见。实现ART留存目标面临的一个挑战是开发、测试和实施针对流动人群并使其坚持终身治疗的项目设计。这应以中断治疗的风险因素为指导,并改善常规信息系统的相互联系,以更好地支持跨复杂护理平台的患者护理。